U.S. patent application number 10/013760 was filed with the patent office on 2006-02-16 for method of inhibiting formation of neisseria gonorrhea and neisseria meningiditis.
Invention is credited to John Docherty.
Application Number | 20060035984 10/013760 |
Document ID | / |
Family ID | 35800809 |
Filed Date | 2006-02-16 |
United States Patent
Application |
20060035984 |
Kind Code |
A1 |
Docherty; John |
February 16, 2006 |
METHOD OF INHIBITING FORMATION OF NEISSERIA GONORRHEA AND NEISSERIA
MENINGIDITIS
Abstract
The present invention provides a method of inhibiting the
formation of pseudorabies particles in a host cell. The method
involves administering an effective amount of a poly-hydroxylated
stilbene, particularly resveratrol, to a herpes virus infected host
cell. The present invention also provides a method of reducing or
inhibiting the growth of Neisseria gonorrhea and Neisseria
meningiditis in vitro and in vivo. The method comprises
administering a composition comprising a therapeutically effective
amount of a tri-hydroxylated stilbene to a growth surface which has
come into contact or could come into contact with the
bacterium.
Inventors: |
Docherty; John; (Kent,
OH) |
Correspondence
Address: |
CALFEE HALTER & GRISWOLD, LLP
800 SUPERIOR AVENUE
SUITE 1400
CLEVELAND
OH
44114
US
|
Family ID: |
35800809 |
Appl. No.: |
10/013760 |
Filed: |
December 11, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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09734444 |
Dec 11, 2000 |
6355692 |
|
|
10013760 |
Dec 11, 2001 |
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Current U.S.
Class: |
514/733 |
Current CPC
Class: |
A61K 31/05 20130101 |
Class at
Publication: |
514/733 |
International
Class: |
A61K 31/05 20060101
A61K031/05 |
Claims
1-8. (canceled)
9. A method of treating a subject with a Neisseria gonorrhea or a
Neisseria meningiditis infection of the eye, said method comprising
administering 3,5,4'-trihydroxystilbene to the eye of the
subject.
10. The method of claim 9, wherein the trans form of
3,5,4'-trihydroxystilbene is administered to the eye the
subject.
11-16. (canceled)
17. The method of claim 9, wherein the cis form of
3,5,4'-trihydroxystilbene is administered to the eye of the
subject.
18-19. (canceled)
20. A method of inhibiting or reducing infection with Neisseria
gonorrhea in the urethra, genitalia, or cervix of a human subject,
comprising: administering a pharmaceutical composition comprising
resveratrol to the urethra, genitalia, cervix, or any combination
thereof of said human subject.
21. The method of claim 20 wherein the pharmaceutical composition
is administered to a mucous membrane of the subject.
22-28. (canceled)
29. A method of treating a human subject infected with Neisseria
gonorrhea, comprising: administering a pharmaceutical composition
comprising a therapeutically effective amount of resveratrol at or
near an infected site of the subject.
30. The method of claim 29 wherein the pharmaceutical composition
is administered via local administration to the genitalia, rectum,
cervix, throat, oropharynx or any combination thereof of the
subject.
31. The method of claim 20, wherein the composition comprises the
trans form of resveratrol.
32. The method of claim 29, wherein the composition comprises the
trans form of resveratrol.
33. A method of inhibiting or reducing development of a Neisseria
meningiditis infection in the eye of a neonate, comprising
administering resveratrol to the eye of the neonate.
Description
BACKGROUND
[0001] The present invention relates to methods of inhibiting
replication of three pathogenic microorganisms, pseudorabies virus,
Neisseria gonorrheae, and Neisseria meningiditis.
[0002] Pseudorabies virus, a member of the Herpesvirus family,
primarily affects swine. Because virus is present in the nasal and
oral discharges of infected pigs, infection is usually transmitted
between pigs by none to nose contact. Contaminated drinking water
and feed buckets may also transmit disease. Clinical symptoms in
pigs can vary from undetectable to death. The extent of the
symptoms depends on the age and immune status of the animal at the
time of infection, the virus dose, route of infection, and strain
of virus. Young pigs may be severely affected with a 100% mortality
in pigs under 2 weeks of age. Piglets may die suddenly or, prior to
death, exhibit symptoms which include fever, loss of appetite,
convulsions, and paddling. The severity of clinical signs decreases
with age, and older pigs may only experience fever and inappetence
of a few days duration.
[0003] Since pseudorabies is a virus infection, antibiotics have no
effect. The primary methods for preventing spread of the disease
involves treatment of environmental surfaces with agents that
inactivate the virus. Examples of such agents are phenolic
compounds, quaternary ammonimum compounds, chlorhexidine diacetate,
iodines, and 5% sodium hydroxide. Vaccines may also be used to
control spread of the disease. Additional methods for inhibiting
replication of the virus, and thereby controlling the spread of the
virus and the severity of the disease in swine exposed to the virus
are desirable.
[0004] Neisseria gonorrhea is a gram negative bacterium that is
pathogenic in humans. The bacterium is spread from person to person
by contact with infected secretions, most often by sexual contact.
Once the pathogen is deposited on a mucosal surface, a complex
series of molecular interactions occur that result in invasion of
mucosal columnar cells. The spectrum of diseases ranges from local
infections of the urethral, cervical, rectal and oropharyngeal
membranes to invasion of the pelvis or epididymis, to invasion of
the blood stream, with or without dissemination to distant organs
such as heart valves, joints, and pericardium. The pathogen may
also infect the conjunctiva. Gonococcal conjunctivitis is most
often contracted by neonates passing through an infected birth
canal, although adults can also be infected.
[0005] The quest for a gonococcal vaccine has been ongoing for many
years with virtually no success. Accordingly, the primary treatment
involves preexposure or postexposure antibiotic prophylaxis. In
addition to antibiotic eyedrops, silver nitrate has also been used
to treat neonatal gonococcal conjunctivitis. Unfortunately, the
bacterium has developed resistance to some of the most common
antibiotics, such as penicillin. Accordingly, additional
compositions for reducing growth of this pathogen is desirable.
[0006] Neisseria meningiditis, another member of the genus
Neisseria, is also pathogenic in humans. The organism is carried on
the nasopharyngeal mucosa of infected individuals and, presumably,
is transmitted from person to person through passage of respiratory
secretions or aeosolized droplets. Although the organism may cause
oropharyngitis, it is primarily a saprophyte that asymptomatically
colonizes the majority of human beings sometime during their lives.
As with other neisserial species, it can sometimes colonize the
genital tract or conjunctiva. On rare occasions, the organism
invades the blood stream. Once the organism has invaded the blood
stream, an overlapping array of clinical outcomes ranging from a
transient bacteremia, to invasion of the meninges, and encephalitis
can occur. Treatment primarily involves administration of
antibiotics. Vaccines are also used to prevent infection.
Unfortunately, the bacterium may develop resistance to the
antibiotics. Moreover, the duration of immunity with the currently
available vaccines is limited. Accordingly, it is desirable to have
new methods for preventing or inhibiting growth of Neisseria
meningiditis.
SUMMARY OF THE INVENTION
[0007] The present invention provides a new method of inhibiting
the formation of infectious pseudorabies virus particles, in a host
cell. The method involves administering a poly-hydroxylated
stilbene, particularly resveratrol, or a derivative thereof to a
pseudorabies virus infected host cell. The poly-hydroxylated
stilbene is administered to the host cell in an amount sufficient
to inhibit replication of the virus in the virus-infected host
cell. Such method is useful for preventing the spread of
pseudorabies virus from a virus-infected host cell to a
non-infected host cell. Such method is also useful for establishing
a model system for studying the molecular events that occur during
replication of pseudorabies virus. In vivo, the method involves
administering a composition comprising a poly-hydroxylated
stilbene, preferably a tri-hydroxylated stilbene, or a derivative
thereof to a non-human animal prior to or shortly after exposure of
the animal to the virus. Such method is useful for reducing the
cytopathic effect of a pseudorabies virus infection.
[0008] The present invention also provides a method of inhibiting
replication of the gram negative bacteria belonging to the genus
Neisseria, particularly Neisseria gonorrhea and Neisseria
meningiditis. Such method involves contacting the bacterium with a
composition containing a tri-hydroxylated stilbene or derivative
thereof. In vivo, such method can be used to treat an individual
who has come in contact with, e.g., a carrier, or an individual who
is expected to come into contact with the bacterium, i.e., an
individual who may be exposed to the carrier. In vivo, such method
comprises administering a composition comprising a therapeutically
effective amount of a tri-hydroxylated stilbene, particularly
resveratrol, or a derivative thereof to said subject.
BRIEF DESCRIPTION OF THE FIGURES
[0009] FIG. 1 is a graph showing the extent of pseudorabies virus
replication in virus-infected cells incubated in medium lacking
resveratrol or containing 50 .mu.g/ml of resveratrol.
DETAILED DESCRIPTION OF THE INVENTION
[0010] In accordance with the present invention, it has been
discovered that tri-hydroxylated stilbenes, particularly
resveratrol has an antimicrobial effect on select pathogenic
microorganisms including pseudorabies virus, Neisseria gonorrhea,
and Neisseria meningiditis. In accordance with the present
invention, it has also been shown that resveratrol at
concentrations ranging from 1 .mu.g/ml to 200 .mu.g/ml of solution
does not inhibit the growth of Eschericia coli, Staphylococcu
aureus, Group A beta-hemolytic Streptococcus, Pseudomonas
aeruginosa or Candida albicans.
Tri-Hydroxylated Stilbenes
[0011] The structural skeleton of the compound employed in the
present methods, i.e., the polyhydroxylated stilbene, comprises two
aromatic rings joined by an ethylene bridge. Preferably, the
compound is a tri-hydroxystilbene, more preferably
3,5,4'-trihdyroxystilbene, which is also known as resveratrol, or a
derivative thereof. Resveratrol in either the cis form or trans
form is suitable. Derivatives of resveratrol as used herein refers
to compounds in which one or two of the hydroxyl functions of
resveratrol are replaced with other moieties such as, for example,
pterostilbene in which the hydroxyl functions at positions 3 and 5
on the disubstituted aromatic ring are methoxylated. Another
example is .beta.-glucoside derivative polydatin or piceid, in
which one of the hydroxyl functions on the disubstituted aromatic
ring is replaced with glucose; as well as polymers of the parent
compound resveratrol. Such polymers have been given the name
viniferins. Methods for producing the hydroxylated stilbenes are
described in Moreana-Manas, M. et al, Anal Quim (1985) 81:157-161;
Jeandet, P. et al, Am J. Enol Vitic (1991) 42:41-6; Goldberg D M et
al. Anal Chem (1994) 66:3959-63, Murakami, S et al, Biochem
Pharmacol. (1992) 44:1947-51; and Thakkar, K et al, J. Med Chem
(1993) 36:2650-51, which are incorporated herein by reference.
Resveratrol and 3,3',4,5'-tetrahydroxy-trans-stilbene, known as
piceatoannol, are also available commercially from Sigma Chemical
Co., St. Louis, Mo.
Methods of Inhibiting Formation of Infectious Pseudorabies Viral
Particles
[0012] In one aspect, the present invention provides a method of
inhibiting formation of infectious pseudorabies viral particles in
a host cell. The method comprises administering a polyhydroxylated
stilbene, preferably a tri-hydroxylated stilbene, or a derivative
thereof to the host cell. The polyhydroxylated stilbene is
administered in an amount sufficient to or effective to inhibit
replication of the pseudorabis virus within the infected cell.
Preferably, the polyhydroxylated stilbene or derivative thereof is
administered to the host cell either prior to infection of the host
cell with the virus or preferably, within six hours after infection
of the host cell with the virus.
[0013] Preferably, the tri-hydroxylated stilbene or derivative
thereof is administered to the host cell by contacting the host
cell with or exposing the host cell to a composition comprising the
tri-hydroxylated stilbene or derivative thereof. For example, in
vitro, the method comprises adding a tri-hydroxylated stilbene to
the culture medium of pseudorabies virus-infected host cells. In
the case of cultured cells, the tri-hydroxylated stilbene is added
to the medium, preferably before the host cells are infected with
the virus or within six hours after the host cells are infected
with the virus. Good results have been obtained by exposing
cultured host cells to the tri-hydroxylated stilbene, resveratrol,
at a concentration which is greater than 1 .mu.g/ml and less than
200 .mu.g/ml of culture medium.
[0014] It has been determined that treatment of cultured cells in
accordance with the present method is non-toxic to cells and blocks
replication of pseudorabies virus at some early stage in it
replicative cycle. It has also been determined that the effect of
resveratrol on pseudorabies virus replication is reversible.
Typical of the herpes viruses, pseudorabies replication occurs in
phases, with each phase being dependent on the successful
completion of the prior phase. The "immediate early phase" occurs
at 1-3 hours after infection and is associated with regulatory and
synthetic events. The "early phase" occurs 3-6 hours after
infection and is also associated with regulatory and synthetic
events, particularly the synthesis of virus DNA. The "late phase"
occurs 6-10 hours after infection and is associated with final
synthetic events and assembly of viral components into infections
virions. Such method is useful for establishing model systems for
studying the molecular events that occur during replication of
pseudorabies virus. For example, mammalian cell cultures incubated
in the presence and absence of resveratrol may be used to identify
cellular factors that are involved in regulating pseudorabies virus
synthetic events. Such cell cultures may also be employed to
characterize the role of psuedorabies virus gene products in the
replication of infectious virus, particularly those proteins and
factors whose function are currently unknown.
[0015] In vivo, the method is used to inhibit the development of or
to reduce the severity of a pseudorabies infection in a mammalian
subject, particularly a non-human mammalian subject. Such method
comprises administering a therapeutically effective amount of the
tri-hydroxylated stilbene or derivative thereof to a mammalian
subject prior to or shortly after exposure to the virus. Such
method is particularly useful for reducing the severity of
infection in a pig and, in some cases, preventing the animal from
becoming a carrier. Since transmission among pigs is typically due
to nose to nose contact, it is preferred that the tri-hydroxylated
stilbene be administered in a composition which enters the pig
through the nose or the oropharynx. For example, the
tri-hydroxylated stilbene may be added to the drinking water or the
feed of animals that may have come into contact with or could come
into contact with the virus. In addition, the tri-hydroxylated
stilbene may be incorporated into an aerosolizable solution or
suspension which is then misted into the nurseries of newborn
piglets.
Method of Inhibiting Growth of Neisseria gonorrheae or Neisseria
meningiditis
[0016] In another aspect, the present invention provides a method
of inhibiting the growth of Neisseria gornorhea and Neissieria
meningiditis. The method comprises administering a tri-hydroxylated
stilbene, preferably resveratrol, or a derivative thereof to a
surface which has come in contact with or could come in contact
with the organism. In vivo, the method, which comprises
administering the tri-hydroxylated stilbene to a mucous membrane of
a human subject, may be used to prevent or reduce the symptoms of
gonnococcal or meningococcal disease in the human subject. The
tri-hydoxylated stilbene or derivative thereof may be incorporated
into a pharmaceutical composition which is applied to the mucous
membrane of a carrier of the bacterium or a person who could come
into contact with the carrier.
[0017] Pharmaceutical compositions used in the present methods
comprise a therapeutically effective amount of a tri-hydroxylated
stilbene preferably resveratrol or a derivative thereof, and a
pharmaceutically acceptable carrier. Preferably, the composition
comprises a relatively inert carrier. Many such carriers are
routinely used and can be identified by reference to pharmaceutical
texts. Examples include polyethylene glycols, polypropylene
copolymers, and some water soluble gels. Such a composition may
also contain diluents, fillers, salts, buffers, stabilizers,
solubilizers, and other pharmaceutically acceptable materials well
known in the art. The term "pharmaceutically acceptable" means a
non-toxic material that does not interfere with the effectiveness
of the anti-microbial activity of the tri-hydroxylated stilbene or
derivative thereof.
[0018] In practicing the present method, a pharmaceutical
composition comprising a therapeutically effective amount of the
hydroxylated stilbene, preferably resveratrol, is applied to a
potential or actual site of infection in the host subject before or
after the host subject is exposed to the bacterium. Such
composition may be used prophylactically to prevent or reduce the
severity of infections of the eye, nose, mouth, throat, oropharynx,
genitalia, and rectum. In the case of oral administration,
dentrifices, mouthwashes, tooth paste or gels, or mouth sprays are
used. Vaginal or rectal administration may be by the usual carriers
such as douches, foams, creams, ointments, jellies, and
suppositories, the longer lasting forms being preferred. Ocular
administration is preferably by ophthalmic ointments or
solutions.
[0019] The pharmaceutical composition may further contain other
agents which either enhance the activity of the tri-hydroxylated
stilbene or complement its activity or use in inhibiting growth of
the gonoccocus or meningococcus. Such additional factors and/or
agents may be included in the pharmaceutical composition to produce
a synergistic effect with the tri-hydroxylated stilbene, or to
minimize side effects.
[0020] Preferably the pharmaceutical composition comprises a
solvent for the tri-hydroxylated stilbene or derivative thereof,
such as, for example, an alcohol. A liquid carrier such as water,
petroleum, oils of animal or plant origin such as peanut oil,
mineral oil, soybean oil, or sesame oil, corn oil, or synthetic
oils may be added. The liquid form of the pharmaceutical
composition may further contain a physiological saline solution,
dextrose or other saccharide solution, or glycols such as ethylene
glycol, propylene glycol or polyethylene glycol. The preparation of
such pharmaceutical composition having suitable pH, isotonicity,
and stability, is within the skill in the art.
[0021] Administration of the pharmaceutical composition to an
uninfected subject is via local administration to a site which has
been or may be contacted with the pathogenic organism. It is
preferred that the pharmaceutical composition be applied prior to
exposure to the targeted pathogen or preferably within 1-24 hours,
more preferably within 1-12 hours after exposure of the uninfected
subject to the pathogenic organsim.
[0022] Administration of the pharmaceutical composition to a
carrier of Neisseria meningiditis is via local administration to
the upper respiratory tract, i.e. ororpharynx. Administration of
the pharmaceutical composition to a carrier of Neisseria gonorrhea
is via local administration to the genitalia, rectum, or
oropharynx.
Dosage
[0023] The tri-hydroxylated stilbene, preferably resveratrol or a
derivative thereof is administered to the host subject in a
therapeutically effective amount. As used herein, the term
"therapeutically effective amount" means the total amount of the
tri-hydroxylated stilbene that is sufficient to show a meaningful
benefit, i.e., prevention or reduction in the extent of infection
by the targeted pathogen or a reduction in the severity of the
symptoms that result from infection with the targeted pathogen. The
dosages of the tri-hydroxylated stilbene, particularly resveratrol,
which can prevent or reduce the severity of an infection with
pseudorabies virus, Neisseria gonorrhea or Neisseria meningididtis
can be determined in view of this disclosure by one of ordinary
skill in the art by running routine trials with appropriate
controls. Comparison of the appropriate treatment groups to the
controls will indicate whether a particular dosage is effective in
preventing or reducing the severity of the infection at the levels
used in a controlled challenge.
[0024] It is contemplated that the various compositions used to
practice the method of the present invention should contain about
0.01 .mu.g to about 10 .mu.g, more preferably about 0.1 .mu.g to
about 1 mg, of the tri-hydroxylated stilbene, most preferably from
about 10 .mu.g to about 100 .mu.g of resveratrol per/ml of the
composition. Although a single administration of the composition
may be sufficient to ameliorate the pathological effects of the
virus or bacteria, it is expected that multiple doses will be
preferred.
[0025] The following examples of methods of using resveretrol to
block formation of infectious psuedorabies virus particles and
growth of Neisseria gonorrhea and Neisseria meningiditis in vitro
are for purposes of illustration only and are not intended to limit
the scope of the claims which are appended hereto.
EXAMPLE 1
Inhibiting Formation of Infectious Pseudorabies Particles by
Treatment with Resveratrol
[0026] Cultures of African green monkey kidney cells (Vero) cells,
obtained from the American Type Culture Collection, Rockville, Md.,
were grown to confluence in Medium 199 supplemented with 5% fetal
bovine serum, 0.075% NaHCO.sub.3, and 50 .mu.g/ml gentamycin
sulfate in 25 cm.sup.2 tissue culture flasks. Cells were infected
with pseudorabies virus at a multiplicity of infection (moi) of one
and incubated at room temperature for one hour to allow for virus
attachment to and penetration of the cell. Under these conditions,
approximately half of the cells are infected with virus.
Thereafter, the cultures were rinsed three time with media and
incubated in medium containing resveratrol at a final concentration
of 50 .mu.g/ml. Stock solutions of the resveratrol, obtained from
Sigma Chemical Co, St. Louis, Mo. were prepared in 100% ethanol and
diluted to the final concentration in tissue culture media. The
maximum concentration of alcohol in the medium was 0.5%. Controls
were treated identically, but were incubated without
resveratrol.
[0027] Upon addition of the medium to the cultures and at 24 hours
time periods thereafter, i.e., 0 hours, 24 hours, 48 hours, and 72
hours after addition of the drug, cells and medium were frozen at
-70.degree. C. Samples were then thawed, sonicated and titrated in
Vero cells to determine the number of plaque forming units (pfu's)
of virus produced by each culture.
[0028] As shown in FIG. 1, the number of pfu's produced in the
control cultures infected with an moi of 1 increases rapidly for 24
hours then slows by 48 hours and 72 hours after infection. At this
time, the system is exhausted, i.e., active virus has infected and
destroyed not only those cells infected during the initial one hour
of incubation but also those cells which became infected with virus
released by the initially-infected cells. The lack of significant
increase observed in the control cultures at 48 and 72 hours after
treatment indicates that the virus production has peaked, due to
the lack of viable cells in which to reproduce.
[0029] As shown in FIG. 1, treatment of cells with 50 .mu.g/ml of
resveratrol inhibited formation of infectious virus particles in
pseudorabies virus infected cells by more than 99% at 24 hours. By
72 hours, infectious pseudorabies virus particles were virtually
undetectable in cultures continuously incubated in the presence of
50 .mu.g/ml of resveratrol.
EXAMPLE 2
Inhibiting Growth of Neisseria gonorrhea by Treatment with
Resveratrol
[0030] Stock solutions of the resveratrol, obtained from Sigma
Chemical Co, St. Louis, Mo. were prepared in 100% ethanol.
Different quantities of the stock solution where added to melted
chocolate agar which was then poured into a petri dish and allowed
to solidify. The final concentration of resveratrol in the agar
ranged from 1 .mu.g to 200 .mu.g/ml. The final concentration of
ethanol in the agar was 0.5%. Control plates containing chocolate
agar and ethanol at a final concentration of 0.5% were also
prepared.
[0031] Neisseria gonorrhea was obtained from patients diagnosed
with gonorrhea. The authenticity of the bacterium was confirmed
utilizing standard microbiological techniques of identification.
Cultures of the bacterial isolate were inoculated onto fresh plates
and then 24 hours later, a suspension was made from isolated
colonies.
[0032] 10 .mu.l aliquots of the suspension were spread evenly
across the surface of samples of solidified control chocolate agar
lacking resveratrol and samples of the chocolate agar containing
resveratrol at final concentrations ranging from 1 to 200 .mu.g/ml.
Thereafter, the samples were incubated at 37.degree. C. with or
without 5% CO.sub.2. All samples were visually examined for growth
of the bacterium 24 hours later to determine the concentration of
resveratol that inhibits growth by 50% (MIC.sub.50) as well as the
concentration which inhibits any visible growth (MIC.sub.100)
EXAMPLE 3
Inhibiting Growth of Neisseria meningiditis by Treatment with
Resveratrol
[0033] A culture of Neisseria meningiditis was obtained from the
American Type Culture Collection. Authenticity of the bacterium was
confirmed utilizing standard microbiological techniques of
identification. Cultures of the bacterial isolate were inoculated
onto fresh plates and then 24 hours later, a suspension was made
from isolated colonies.
[0034] 10 .mu.l aliquots of the suspension were spread evenly
across the surface of samples of solidified control chocolate agar
lacking resveratrol and samples of the chocolate agar containing
resveratrol at final concentrations ranging from 1 to 200 .mu.g/ml.
Thereafter, the samples were incubated at 37.degree. C. with or
without 5% CO.sub.2. All samples were visually examined for growth
of the bacterium 24 hours later to determine the resveratrol
concentration that inhibits growth by 50% (MIC.sub.50) and the
resveratrol concentration which inhibits any visible growth
(MIC.sub.100)
Results
[0035] The results, shown in Table 1 below, demonstrate that
resveratrol at a concentration of 25 .mu.g/ml inhibited growth of
Neisseria gonorrhoeae by 50%, while resveratrol at a concentration
of 75 .mu.g/ml inhibited growth of this pathogen by 100%.
Resveratrol at a concentration of 100 .mu.g/ml inhibited growth of
Neisseria meningiditis by 50%, while resveratrol at a concentration
of 125 .mu.g/ml inhibited growth of this pathogen by 100%.
TABLE-US-00001 TABLE 1 The Inhibitory Concentration (IC) of
Resveretrol on Bacteria and Yeast In Vitro Microorganism
.mu.g/ml.sup.a .mu.g/ml.sup.b Neisseria gonorrhea 25 75 Neisseria
meningitidis 100 125 Escherichia coli >200 >200
Staphylococcus aureus >200 >200 Group A Beta Streptococcus
>200 >200 Pseudomonas aeruginosa >200 >200 Candida
albicans >200 >200 IC.sub.50 is a 50% reduction in bacterial
growth after 24 hours. IC.sub.100 is a complete inhibition of
bacterial growth after 24 hours.
IC.sub.50 is a 50% reduction in bacterial growth after 24
hours.
[0036] IC.sub.100 is a complete inhibition of bacterial growth
after 24 hours.
* * * * *